Review Article

A Gout Flare Caused by the Administration of Platelet Rich Plasma:

A Clinical Case
1Department
of Internal Disease Propaedeutic and Rheumatology, Medical University of Plovdiv, Bulgaria
*Correspondence author: Plamen Todorov, Department of Internal Disease Propaedeutic and Rheumatology, Medical University of Plovdiv, Bulgaria;
Citation: Todorov P, et al. A Gout
Flare Caused by the Administration
of Platelet Rich Plasma: A Clinical
Case. J Reg Med Biol Res. 2023;4(1):1-
5.
https://doi.org/10.46889/JRMBR.2023.
4103
Received Date: 11-02-2023
Accepted Date: 24-02-2023
Published Date: 05-03-2023
Copyright: © 2023 by the authors.
Submitted for possible open access
publication under the terms and
conditions of the Creative Commons
Attribution (CCBY) license
(https://creativecommons.org/li
censes/by/4.0/).
Plamen Todorov1*, Anastas Batalov1
Email: drtodorovplamen@gmail.com
Abstract
The therapy with Platelet Rich Plasma (PRP) administered in degenerated or injured
musculoskeletal tissues is a new and promising regenerative treatment option. Traditionally, it
is considered that as PRP represents an autologous (to the patient) blood product, the potential
for serious side effects is neglectable. Consequently, it is important that any significant negative
consequences are well described. We present a fifty-five years old male patient, complaining of
pain and stiffness in his right ankle joint due to multiple traumas during his earlier sport career.
He had no any contraindications and PRP was injected intraarticularly under ultrasound
guidance. On the next day, the patient developed an intensive pain and swelling in the regions
of the right ankle and the dorsum of the right foot. The acute phase reactants were elevated and
there was no leukocytosis. On ultrasound examination, there was an effusion in the tibiotalar
and talonavicular joints. Arthrocentesis was performed and the microscopic examination
revealed the typical needle shaped monosodium urate crystals inside the joint fluid and no
bacteria. Consequently, the diagnosis of acute gouty flare was made (the patient has a history
of gout, but did not have any flares in the past two years). As PRP concentrate contains
naturally many proinflammatory molecules, we speculate that some of them may activate the
macrophages that residue normally in the synovium and the capsule of the injected joint. The
activated macrophages further may react to the MSU crystals deposited there, leading to the
development of a gouty flare. In conclusion, the possibility of a flare should be explained to
gouty patients, candidate for PRP treatment.

Keywords: Platelet Rich Plasma; Gout; Flare

Introduction
The Platelet Rich Plasma (PRP) therapy offers a new and potentially revitalizing option in the treatment of degenerative
rheumatic diseases. Since its first conceptualizing in the 1990s, this method was increasingly used in the rheumatological and
orthopaedic medicine practice [1]. Traditionally, it is considered that as the PRP represents an autologous (to the patient) blood
product, the potential for any side effects or negative consequences of this treatment virtually does not exist. Consequently, it is
very important that any significant side effects are described and distributed to the knowledge of the physicians practicing this
therapeutical method.

In the current clinical case, we describe an intensive gout flare, directly connected with the administration of PRP for an ankle
joint osteoarthritis and ligamentous injury.

Case Description
Fifty-five years old male patient was consulted due to constant pain and stiffness in his right ankle joint. He is an ex professional
comparator in sport orienteering and he relate his ankle complaints with multiple traumas and sprains of the ankle supporting

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ligaments throughout his sport career and to the substantial weight gain in the recent years. The patient has tried multiple courses
of physiotherapy treatments, but he still needs frequent intake of NSAIDS for his pain. At clinical examination, the patient has
limited range of motion in his right tibio-talar joint, pain on palpation along the joint line, as well as pain on varus and valgus
stress of the ankle. The X rays showed osteoarthritis of the right tibio-talar joint with narrowing of joint space and subchondral
osteosclerosis. The ultrasound of the right ankle showed non-uniform thinning of the cartilage along with ligamental pathology
(thickened and hypoechoic talo-fibular, deltoid and calcaneo-fibular ligaments), no synovitis or joint effusion were evident. At
the laboratory tests there are no signs of inflammation, the number of platelets in the peripheral blood meets the requirements
for a PRP treatment.

After discussion on the therapeutic options, the patient was offered a treatment of his ankle condition with PRP injections, which
the patient accepted and signed an inform consent form. The standard procedure for this treatment at our institution was
followed: 22 ml of venous blood was drowned out in a 25 ml sterile system for platelets separation that was prefilled with a 3 ml
of 1% sodium citrate. After that, the system was placed in a centrifuge and spined double times (respectively 8 and 3 minutes)
at 3500 RPM according to the manufacturer instructions (SWS, South Korea). The PRP produced by this process was transferred
in a 5 ml sterile syringe and then injected under ultrasound guidance intraarticularly in the patients’ right tibio-talar joint, as well
as periarticular along the predefined damaged ligaments. Aseptic conditions were maintained all through the procedure. There
were no any side effects reported and the patient left the clinic with an advice to restrain from greater physical activity the
following days.

On the next day, the patient called the clinic and complained of a very intensive pain, swelling and feeling of warmth in the
regions of the right ankle and the dorsum of the right foot. He could barely walk due to the pain. The patient was invited to the
clinic. On the clinical examination there was a substantial swelling in the right ankle and foot, the overlaying skin was warm, the
area was tender and painful on palpation, the range of motion in the tibio-talar and talonavicular joints - decreased. According
to the patient, the current symptoms resembled very much the gout flares that he has experienced before, but not in the last two
years when there were no attacks.

The ultrasound examination showed effusion in patient’s right tibiotalar and talonavicular joints with the presence of
hyperechoic amorphous material in the fluid, as well as subcutaneous oedema. The laboratory results reviled elevated levels of
the CRP and ESR, no leukocytosis and borderline serum uric acid. The diagnosis of an acute crystal arthritis flare gout was made.
In the differential diagnostic plane, the possibility of septic iatrogenic arthritis was discussed but there was no fever, systemic
signs, leukocytosis. Anyway, an ultrasound guided arthrocentesis with aspiration of the synovial fluid was carried out. The
sample was examined under polarized light microscope and the typical needle shaped MSU crystals were seen (Fig. 1-3). The
fluid was also sent for a microbiological study and no bacteria growth was detected. A therapy with colchicum was initiated, the
patient advised to follow RICE regimen and to report any worsening of the condition. In one week, the symptoms gradually
improved and the patient returned to work and resume everyday activities.

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Figure 1: Patent’s swollen right ankle joint, note normal metatarsophalangeal joints.

Figure 2: Longitudinal ultrasound image across the right ankle joint showing effusion in the Tibiotalar (TTJ) and Talonavicular
(TNJ) joints (arrows), note the hyperechoic material inside the effusion in the tibiotalar (asterisks) and the Subcutaneous
Oedema (SCO).

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Figure 3: Needle shaped MSU crystals from the patient’s tibiotalar joint effusion under light microscopy.

Discussion
The uric acid arthritis (gout) is the most frequent among the crystal induced arthritis. It is caused by accumulation and deposition
of Monosodium Urate (MSU) crystals in the articular and periarticular tissues. Gout is a frequent disease, for example it was
found to affect 3,9% of the population in the USA [2]. The typical course of the disease includes sudden acute flares of pain which
are followed by symptomless period with variable length (sometimes years as in the present patient). The flares are caused by
different stimuli- stress, dehydration, diet mistakes, infections, all of which could decrease the stability of the intratissue MSU
deposits. The recognition of the naked MSU crystal by Toll-like receptor, which are normally involved in triggering innate host
defence responses to infectious pathogens, was recently discovered to be a primary trigger of the inflammatory tissue reactions
associated with gouty arthritis. Thus, macrophages can recognize and contact with the MSU crystals, got activated and start an
intense and rapid inflammatory reaction [3]. During the flare, the affected joints are extremely painful, swollen and hot, making
septic arthritis the main differential diagnosis consideration. The treatment of the acute flare is with colchicum, corticosteroids,
ACTH, NSAIDs, IL 1 blockers, RICE regimen [2,3]. In our case, the medical treatment included only colchicum and RICE, as
NSAIDs and corticosteroids are known to interfere negatively with the regenerative capabilities of the PRP (1), while IL 1 blockers
are not available in our country.

The PRP therapy is part of the conception of the so-called Orth biologic medications which are administrated to promote tissue
regeneration [4]. The proteomic analysis showed that the activated platelets can release up to 3000 bioactive proteins [5]. They
regulate in a synergetic way numerous molecular pathways included in the chemotaxis, cell proliferation and specialization, neo
angiogenesis and synthesis of the extracellular matrix. Some of these bioactive molecules, although important in tissue
repairment are proinflammatory in nature [5,6].

Traditionally, the PRP treatment is considered safe, with minimal risk of side effects, provided that good aseptic environment
and technic of intervention are implemented. In the literature the main side effect described is postprocedural pain with various
intensity, but generally short-lived [7].

Our literature search in PubMed did not revile any reports on gout flares following PRP administration. Yet, we think that, in
our patient the PRP application could have caused the observed intensive gout flare due to several possible mechanisms. Firstly,
some of the proinflammatory molecules, contained naturally in the platelet concentrate may activate the macrophages that

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residue normally in the synovium and the capsule of the injected joint. These activated macrophages then may react to the MSU
crystals deposits that are presented in the articular and periarticular tissues of the patient. This interaction may lead to further
and sustained macrophages activation and development of a true gout flare. On the other hand, the low-grade inflammation that
always follows the intraarticular/ periarticular degranulation of the injected large number of platelets during the PRP
administration, could cause destabilization of the disposable MSU crystals, their contact and interaction with the macrophages
and eventually to an acute crystal flare. In addition, it is known that sometimes small sport or hobby related injuries of the foot
may provoke a flare in gout patients. As in trauma there is some intratissue bleeding, the mechanism of developing a flare due
to a traumatic episode and due to PRP administration could be similar.

Conclusion
To the best of our knowledge, this is the first report of a gout flare as a direct consequence of a PRP concentrate administration.
The affected joint was the same that was injected with the PRP. Considering the growing popularity, availability and usage of
PRP treatment among physicians dealing with musculoskeletal problems, it is mandatory that any significant side effects of this
therapy is marked and described. In our case, we believe that there was a direct relation between the administrated PRP injection
to the patient’s ankle joint and ligaments and the acute gout flare affecting the same that joint. Although the evolution of this
side effect was favourable, it still caused considerable pain, anxiety and limitations in the daily life of the patient, as well as
required additional time and resources from the treating physician. Knowing the possibility of causing an acute flare, the
treatment with PRP should be administrated carefully in patients with known diagnosis of gout (although currently
asymptomatic) and the possibility of a flare explained to them. In addition, a colchicum prophylaxis could be considered in high
risk (i.e., those with recent or numerous flares) gout patients scheduled for a PRP treatment.

Conflict of Interest
The authors have no conflict of interest to declare.

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conservative treatment in orthopaedics: a systematic review and meta-analysis. Blood Transfusion. 2018;16(6):502-13.

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